The present invention relates to prostaglandin and/or prostamide (as well as to esters, salts and derivatives thereof) drug delivery systems for intraocular use. Prostaglandins are a class of pharmacologically active hormone like substances made in various mammalian tissues, which are derived from arachidonic acid, and mediate a wide range of physiological functions including blood pressure, smooth muscle contraction and inflammation. Examples of prostaglandins are prostaglandin E1 (alprostadil), prostaglandin E2 (dinoprostone), latanoprost and travoprost. Latanoprost and travoprost are actually prostaglandin prodrugs (i.e. 1-isopropyl esters of a prostaglandin) however, they are referred to as prostaglandins because they act on the prostaglandin F receptor, after being hydrolyzed to the 1-carboxylic acid. A prostamide (also called a prostaglandin-ethanolamide) is a prostaglandin analogue, which is pharmacologically unique from a prostaglandin (i.e. because prostamides act on a different cell receptor [the prostamide receptor] than do prostaglandins), and is a neutral lipid formed a as product of cyclo-oxygenase-2 (“COX-2”) enzyme oxygenation of an endocannabinoid (such as anandamide). Additionally, prostamides do not hydrolyze in-situ to the 1-carboxylic acid. Examples of prostamides are bimatoprost (the synthetically made ethyl amide of 17-phenyl prostaglandin F2α) and prostamide F2α. The drug delivery systems of our invention can be a drug containing implant or implants or a plurality of drug containing microspheres (synonymously “microparticles”). The drug delivery system can be used therapeutically to treat an ocular disease or condition.
Glaucoma is a disease of the eye characterized by increased intraocular pressure. Glaucoma can be classified as primary or secondary. Primary glaucoma in adults (congenital glaucoma) may be either open-angle or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular diseases such as uveitis, intraocular tumor or an enlarged cataract.
Certain prostaglandins and their analogs and derivatives, such as the PGF2α derivative (sometimes referred to as prostaglandin F2α analogue) latanoprost, sold under the trademark Xalatan®, have been used to treat ocular hypertension and glaucoma. Unfortunately, when topically administered (i.e. as eye drops) latanoprost can have the undesirable side effects of changing the patient's eye color (by increasing iris brown pigment) and causing hyperemia (eye redness or inflammation). Hence, topical administration of latanoprost can be undesirable for both cosmetic and patient comfort reasons.
Intraocular prostaglandin and prostamide implant and microspheres are disclosed by U.S. patent application Ser. Nos. 11/368,845; 11/303,462, and; 10/837,260.
Thus it would be advantageous to provide sustained release latanoprost containing implants and microspheres for intraocular (as opposed to topical) therapeutic use to treat glaucoma, with few or no negative side effects, such as no or substantially no change to iris pigmentation or hyperemia. Such implants or microspheres by releasing the drug over a multiday period can provide an alternative to daily topical administration of latanoprost eyedrops to lower intraocular pressure (“IOP”), thereby treating glaucoma with increased patient compliance (since daily dosing is not required) using a sustained release formulation (latanoprost containing microspheres).